Tedizolid showed improved GI safety profile vs. linezolid

PHILADELPHIA — Novel oxazolidinone antibacterial tedizolid for treatment of patients with acute bacterial skin and skin structure infections showed a better gastrointestinal adverse event profile compared with linezolid, according to phase 3 study data presented at IDWeek 2014.

Researchers compared the gastrointestinal adverse event outcomes of 1,324 patients who participated in the multinational ESTABLISH-1 and -2 trials, half of whom were randomly assigned to receive 200 mg tedizolid once daily for 6 days, and half who received 600 mg linezolid twice daily for 10 days. They then evaluated the respective safety profiles by assessing AEs, clinical chemistry and hematologic laboratory results vital signs, electrocardiograms, and physical exams.

GI disorders were the most commonly reported treatment-related AEs, occurring in 16% of the tedizolid group, compared with 23% of the linezolid group. The lower incidence of GI AEs with tedizolid vs. linezolid was consistent across subgroups except for patients with moderate to severe renal impairment. The most frequently reported GI AEs were nausea, diarrhea and vomiting. Diarrhea was mild in 84.6% of the tedizolid group, compared with 85.7% of the linezolid group and it was not severe in any patients. Likewise, nausea was mostly mild (79.6% vs. 77.7%) as was vomiting (68.4% vs. 72.9%). Onset of GI AEs usually occurred within the first 6 days of treatment (7.1% vs. 10.6%).

The researchers concluded that tedizolid had an improved GI AE profile compared with linezolid at the doses tested, and that “these findings suggest that the more favorable GI tolerability profile of tedizolid might be explained by pharmacologic differences rather than differences in duration of exposure.”

For more information:

Fang E. Abstract 263. Presented at: IDWeek, Oct. 8-12, 2014; Philadelphia, PA.

Disclosure: This study was funded by Cubist Pharmaceuticals.